This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goals of the NIH-funded TrialNet Natural History Study of the Development of T1D are to both gain information about the pathogenesis and natural history of T1D and to facilitate the recruitment and assessment of individuals who might qualify for T1D prevention trials. The TrialNet Natural History Study of the Development of T1D is divided into three phases: Screening (Phase 1), Baseline Risk Assessment (Phase 2) and Follow-up Risk Assessments (Phase 3). Phase 1 involves screening for the presence of autoantibodies associated with T1D. Individuals who are positive for a single biochemical autoantibody, on two separate blood samples during Screening will be eligible for entry into Phase 2 of the study. Individuals positive for at least two biochemical autoantibodies on the first blood sample obtained will be eligible for entry into Phase 2. Baseline Risk Assessment will include an oral glucose tolerance test (OGTT), HbA1c, ICA and HLA typing. A 20-minute intravenous glucose tolerance test (IVGTT) for First Phase Insulin Response (FPIR) may also be performed. Upon completion of Phase 2, participants will be classified into one of three risk categories for the occurrence of T1D within five years. Individuals who complete Phase 2 will then be eligible for Phase 3 and they will be seen at six-month intervals for five years. The primary study outcome is T1D by the American Diabetes Association criteria.